Glycosyltransferase B4GALNT2 as a Predictor of Good Prognosis in Colon Cancer: Lessons from Databases.

Michela Pucci,Fabio Dall’Olio,Nadia Malagolini

doi:10.3390/ijms22094331

Michela Pucci, Fabio Dall’Olio + Show 1 more

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https://doi.org/10.3390/ijms22094331

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Abstract

Background: glycosyltransferase B4GALNT2 and its cognate carbohydrate antigen Sda are highly expressed in normal colon but strongly downregulated in colorectal carcinoma (CRC). We previously showed that CRC patients expressing higher B4GALNT2 mRNA levels displayed longer survival. Forced B4GALNT2 expression reduced the malignancy and stemness of colon cancer cells. Methods: Kaplan–Meier survival curves were determined in “The Cancer Genome Atlas” (TCGA) COAD cohort for several glycosyltransferases, oncogenes, and tumor suppressor genes. Whole expression data of coding genes as well as miRNA and methylation data for B4GALNT2 were downloaded from TCGA. Results: the prognostic potential of B4GALNT2 was the best among the glycosyltransferases tested and better than that of many oncogenes and tumor suppressor genes; high B4GALNT2 expression was associated with a lower malignancy gene expression profile; differential methylation of an intronic B4GALNT2 gene position and miR-204-5p expression play major roles in B4GALNT2 regulation. Conclusions: high B4GALNT2 expression is a strong predictor of good prognosis in CRC as a part of a wider molecular signature that includes ZG16, ITLN1, BEST2, and GUCA2B. Differential DNA methylation and miRNA expression contribute to regulating B4GALNT2 expression during colorectal carcinogenesis.

Highlights

IntroductionGlycosylation changes consist of up- or downregulation of numerous carbohydrate structures affecting tumor invasion and progression [2,3,4]
We showed that B4GALNT2 mRNA expression exhibits a prognostic predictive potential in CRC much better than that of all of the glycosyltransferases tested and even better that that of many oncogenes and tumor-suppressor genes
Patient stratification according to B4GALNT2 expression revealed that High B4GALNT2 expressers (HBE) group displayed a concomitantly high level of other genes associated with positive prognosis, such as ZG16, ITLN1, BEST2, and GUCA2B. (Table 1)

Summary

Introduction

Glycosylation changes consist of up- or downregulation of numerous carbohydrate structures affecting tumor invasion and progression [2,3,4]. The Sda antigen is a carbohydrate structure expressed on erythrocytes and a few other tissues in the vast majority of individuals. The minimal structure of the Sda antigen consists of a α2,3-sialylated galactose to which a GalNAc residue is β1,4-linked (Figure 1) [5]. The few Sda -negative individuals display missense mutations in the C-terminal portion of the

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